Water-in oil lotion containing corticosteroid

ABSTRACT

PCT No. PCT/EP94/04288 Sec. 371 Date Aug. 26, 1996 Sec. 102(e) Date Aug. 26, 1996 PCT Filed Dec. 22, 1994 PCT Pub. No. WO95/17883 PCT Pub. Date Jul. 6, 1995The application is directed to a water-in-oil lotion containing hydrocotisone-21-acetate-17-propionate and one of four compositions containing a water-in-oil emulsion. The lotion is suitable for use on dry skin, it has good spreadability on large surface areas and it is dermatologically acceptable.

The present invention concerns a new type of lotion containing acorticosteroid as active ingredient.

Use is often made of creams as therapeutic vehicles containingcorticosteroids. These creams incorporate either oil-in-water orwater-in-oil emulsion systems.

For example, EP-A-0 217 146 discloses an oil-in-water cream containing ahydrocortisone diester. However, oil-in-water creams play a minor rolein corticosteroid therapies, since most inflammatory processes aretriggered when skin is dry. Accordingly, oil-in-water emulsions(containing water in the external phase of the emulsion) lend themselvesto this application only in a limited manner.

Use is more often made of water-in-oil creams (containing oil in theexternal phase of the emulsion). Because of their thick consistency and,consequently, of the difficulty with which they are spread, they havethe disadvantage of being unsuited to application on large surfaceareas. In addition, they leave an unctuous film on the skin, acosmetically-adverse phenomenon. A water-in-oil emulsion-based creamcontaining hydrocortisone diester as active ingredient is, for example,described in Patent No. EP-A-0 217 141. "Stabilized" creams(water-in-oil emulsions) containing corticosteroids are described, forexample, in U.S. Pat. No. 4,284,630.

These two problems, i.e., poor spreadability on large surface areas andcosmetic unacceptableness, also apply to a greater degree to a thirdtype of topical preparation, i.e., creams such as ointments having avaseline/paraffin base (fatty ointments). In addition to these problems,these preparations soil linen and clothing that has come into contactwith skin treated with them.

A fourth type of vehicle intended for corticosteroid therapy consists ofliquid oil-in-water liquid emulsions, and thus, lotions. The scope ofapplication of these products is similar to that of oil-in-water creams.Oil-in-water lotions nevertheless exhibit the same basic problem asoil-in-water creams. They are not suitable for use on dry skin, which ismost often encountered when these products are indicated. Consequently,the field of application of these lotions is extremely limited, despitetheir general aptitude for application on large surface areas.

Tinctures and tinctures solidified using gelling agents form a fifthtype of base for corticosteroids. In this case, these tinctures aresolutions, most often ethanol-, isopropanol/propylene glycol-, orpolyethylene glycol/water-based. They are often, but erroneously, termedlotions, even though they are not constituted by emulsion systems. Whilethese lotions contain, in addition, a surface-active substance, thissubstance is used only to solubilize the minimally-solublecorticosteroid. Such a tincture, is, for example, described (as a"lotion") in patent EP-A-0 292 893.

The preceding description shows that, to date, there is no vehicle forcorticosteroids which meets the following requirements:

suitability for use on dry skin;

spreadability on large surface areas;

dermatological acceptability.

Water-in-oil lotions alone lend themselves to these purposes. To date,they have not been used in corticosteroid therapy. Even in the cosmeticindustry, water-in-oil lotions tend to separate during storage into anoil and an aqueous phase. Consequently, they cannot be produced by"diluting" a water-in-oil cream with water. To obtain a water-in-oillotion, a complex combination of multiple emulsifiers withspecially-adapted lipophilic compounds proves necessary.

Use must be made of combinations of emulsifiers, because it is hardlypossible to produce a stable water-in-oil lotion based on only one ofthe emulsifiers indicated above. Water-in-oil emulsifiers (or mixturesthereof) constitute new substances that are particularly well-adapted towater-in-oil lotions. They are not identical to the emulsifiers widelyused in water-in-oil creams, such as sorbitan oleates and sorbitanstearates (Span (R) products). The latter (see U.S. Pat. No. 4,284,630)can be used solely for preparing water-in-oil creams.

As regards a water-in-oil lotion of this kind containing acorticosteroid as active ingredient, consideration must be given to thefact that most emulsifiers and stabilizers potentially usable inwater-in-lotions tend to cause decomposition of the corticosteroid theycontain. The stability during storage of the active substance necessaryfor a therapeutic product is thus rendered doubtful. The phrase"necessary stability during storage" signifies that the water-in-oillotion as well as the active substance exhibit the preservabilityrequired for a drug, and thus a life of at least 3 years, even at hightemperatures (greater than 30° C.).

Patent No. DE-A-28 26 257 discloses the corticosteroidhydrocortisone-21-acetate-17-alpha-propionate.

The invention is intended to propose a water-in-oil lotion containinghydrocortisone-21-acetate-17-alpha-propionate, exhibiting good stabilityof the liquid emulsion, while at the same time providing goodpreservability of the active substance during storage and provingoptimally suitable for therapy using corticosteroids in cases of dryskin and for application on large surface areas.

This purpose is achieved using water-in-oil lotions having the followingcompositions A, B, C, or D with combinations of the water-in-oilemulsifiers a) to d).

    ______________________________________                                        A.                                                                            Emulsifier combination a) % by weight                                         ______________________________________                                        a.sub.1 : methoxypolyethylene glycol/dodecyl glycol polymer                                             1-10                                                a.sub.2 : hydroxyoctacosanyl hydroxy stearate                                                           0.5-10                                              a.sub.3 : polyethylene glycol/dodecylglycol copolymer                                                   1-10                                                esters of fatty acids and/or fatty alcohols                                                             1-30                                                liquid paraffin           1-30                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                hydrocortisone-21-acetate-17-propionate                                                                 0.001-3                                             preservative               0-2.5                                              water                     50-85                                               ______________________________________                                        B.                                                                            Emulsifier combination b)                                                     ______________________________________                                        b.sub.1 : esters of fatty acids saturated with glycerol                                                 0.5-10                                              b.sub.2 : polyethoxylated fatty acids                                                                    1-7.5                                              esters of fatty acids and/or fatty alcohols                                                             1-30                                                liquid paraffin           1-30                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.1-2                                               hydrocortisone-21-acetate-17-propionate                                                                 0.001-3                                             preservative               0-2.5                                              water                     50-85                                               ______________________________________                                        C.                                                                            Emulsifying combination c)                                                    ______________________________________                                        c.sub.1 : polyoxypropylene-polyoxyethylene-glycerol-sorbitan-                                           0.5-10                                              hydroxyisostearate                                                            C.sub.2 : polyethoxylated fatty acids                                                                   0.5-7.5                                             esters of fatty acids and/or fatty alcohols                                                             1-30                                                liquid paraffin           1-30                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.1-2.0                                             hydrocortisone-21-acetate-17-propionate                                                                 0.001-3                                             preservative               0-2.5                                              water                     50-85                                               ______________________________________                                        D.                                                                            Emulsifying combination d)                                                    ______________________________________                                        d.sub.1 : glycerol sorbitan oleostearate                                                                0.5-7.5                                             d.sub.2 : polyethoxylated fatty acids                                                                   0.5-10                                              esters of fatty acids and/or fatty alcohols                                                             1-30                                                liquid paraffin           1-30                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.1-2                                               hydrocortisone-21-acetate-17-propionate                                                                 0.001-3                                             preservative               0-2.5                                              water                     50-85                                               ______________________________________                                    

Each of the compositions A to D may, as required, contain additives,and, in addition to the emulsifying combination indicated, one orseveral of the other constituents a₁ to d₂, or one or several of theemulsifying combinations a) to d) mentioned above.

In the lotions containing compositions A, B, C, or D, the water-in-oilemulsifying combinations a) to d) are composed of emulsifiers,stabilizers, thickening agents, and complex emulsifying systems a₁, a₂,etc. to d₁, d₂ as constituents.

Constituent a₁ is preferably a non-ionic water-in-oil emulsifiercontaining approximately 22 ethylene glycol repeating structures. Theseemulsifiers are sold under the tradename Elfacos E 200 (Akzo Chemie, TheNetherlands).

The constituent a₂ acts as a consistency regulator. These products aresold under the tradename Elfacos C26 (Akzo Chemie, The Netherlands).

The constituent a₃ is preferably a non-ionic water-in-oil emulsifierhaving approximately 20 to 45 ethylene glycol repeating structures andan HLB value of about 7. These emulsifiers are sold under the tradenamesElfacos ST 9 and Ellacos ST 37 (Akzo Chemie, The Netherlands).Furthermore, they are described in the literature mentioned above.

Constituent b₁ is a non-ionic water-in-oil emulsifier preferably havinga molecular weight of about 630, and HLB value of about 4.5, and awax-like consistency. These products are sold under the tradenameArlacel 986 (ICI Europa Ltd., Belgium).

Constituent b₂ is preferably a non-ionic saturate water-in-oilemulsifier having a molecular weight of approximately 1,245 and an HLBvalue of about 6.4. Such products are sold, most notably, under thetradename Arlacel 989 (ICI) or Cremophor WO 7 (BASF).

Constituent b₂ corresponds to constituents c₂ and d₂.

Constituent c₁ is a non-ionic saturate water-in-oil emulsifier. Theseproducts are also sold under the tradename Arlacel 780 (ICI).

The preferred esters of fatty acids include isopropyl palmitate,isopropyl myristate, isopropyl isostearate, myristyl myristate,2-cetylhexyl palmitate (Cegesoft sold by the Henkel Company), isooctylstearate (Cetiol 868, sold by the Henkel Company), the decylic ester ofoleic acid (Cetiol V), and the cetyl ester of palmitic acid (Cutina CP,sold by the Henkel company).

The preferred fatty alcohols include myristic alcohol, cetyl alcohol,stearyl alcohol, cetostearyl alcohol, behenyl alcohol, and2-octyldodecanol (Eutanol G).

The paraffin chosen is preferably a highly liquid paraffin, as requiredin combination with a semi-solid paraffin (vaseline), a solid paraffin,or microwaxes. Linear and branched paraffins are especially preferred.

One suitable sorbitol solution is, for example, a 70% aqueous solution.Products of this type are sold, most notably, under the names "Kadon F,""Karion F flussig SK," or "Karion F flussig kosmetik" (E. Merck,Germany).

The lotions preferably contain hydrocortisone-21-acetate-17-propionatein a concentration of 0.001 to 1% by weight, in particular from 0.01 to0.3 by weight, always in relation to the total weight.

Special preference is given tohydrocortisone-21-acetate-17-alpha-propionate in a proportion of 0.025to 0.2% by weight, in particular approximately 0.13% by weight, alwaysin relation to the total weight of the lotion.

Special preference is accorded to lotions incorporating the followingconstituents and, as required, additives.

    ______________________________________                                        A'.                                                                           Emulsifier combination a) % by weight                                         ______________________________________                                        a.sub.1 : methoxypolyethylene glycol/dodecylglycol polymer                                               2-7.5                                              a.sub.2 : hydroxyoctacosanylhydroxystearate                                                             1-5                                                 a.sub.3 : polyethylene glycol/dodecylglycol copolymer                                                    2-7.5                                              esters of fatty acids     1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        B'.                                                                           Emulsifier combination b)                                                     ______________________________________                                        b.sub.1 : esters of fatty acids saturated with glycerol                                                  2-7.5an                                            b.sub.2 : polyethoxylated fatty acids                                                                   1-5                                                 esters of fatty acids     1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        C'.                                                                           Emulsifying combination c)                                                    ______________________________________                                        c.sub.1 : polyoxypropylene-polyoxyethylene-glycerol-sorbitan-                                            2-7.5                                              hydroxyisostearate                                                            C.sub.2 : polyethoxylated fatty acids                                                                   1-5                                                 esters of fatty acids     1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        D'.                                                                           Emulsifying combination d)                                                    ______________________________________                                        d.sub.1 : glycerol sorbitan oleostearate                                                                1-5                                                 d.sub.2 : polyethoxylated fatty acids                                                                   2-8                                                 esters of fatty acids     1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                    

To adjust the pH to a preferred value of 4 to 5, the lotion according tothe invention may contain small quantities of acidic additives, forexample from about 0.01 to about 5% by weight. To this end, carboxylicacids such as succinic acid, lactic acid, citric acid, or phosphoricacid and the salts thereof are suitable for use as buffers.

Preservative and stabilizers can also be added. Suitable substancesinclude parabene, benzalkonium chlorides, p-chloro-m-cresol, benzoicacid, sorbic acid, phenoxyethanol, benzyl acid, butyl hydroxyanisol andbutyl hydroxytoluene, tocopherol acetate, ascorbyl palmitate, andmixtures thereof. These substances may be added in a proportion of from0.01 to 2.5% by weight.

Emulsifiers suitable for water-in-oil lotions containing corticosteroidsconsist partially of very complex compositions having low HLB values, aswell as of mixtures thereof. The choice of emulsifiers was made in orderto produce a water-in-oil lotion proving stable for several years athigh temperatures and compatible with the respective active ingredientsto obtain stabilization of the active ingredients during the periodindicated.

The fatty phase of the water-in-oil lotion consists, for example, of abalanced mixture of liquid paraffins having a linear or branched chain,of natural and synthetic esters, of fatty acids having a linear orbranched chain, whether saturated or unstaturated with monovalent orpolyvalent alcohols (for example, isopropyl palmitate, isopropylmyristate, isopropyl stearate, isopropyl isostearate, myristylmyristate, cetyl palmitate, oleyl oleate, triglycerides having a mediumchain, peanut oil, olive oil, castor oil, hydrogenated castor oil),fatty acids (for example, linoleic acid, oleic acid), and fatty alcohols(for example, myristic alcohol, cetostearyl alcohol), octyl dodecanol,and squalene in a proportion of 1 to 30% by weight, for example.

The lotions according to the invention may contain other additives.

The aqueous phase contains, for example, polyvalent alcohols (forexample, glycerine, propylene glycol, 1,3-butylene glycol, andpolyethylene glycols), saccharide alcohols (for example, sorbitol andxylitol), lecithins (for example, soy lecithin and ovolecithin), orphosphatidyl choline and dipalmitoyl phosphatidyl choline compounds, forexample in a proportion of 1 to 10% by weight.

With the new lotion according the invention, the invention discloses anew water-in-oil lotion containinghydrocortisone-17-propionate-21-acetate which is characterized by a goodactivity level, high dermatological acceptability, and a high degree ofstability during storage.

In comparison with a water-in-oil cream, the water-in-oil lotion has thesignificant advantage of being rapidly absorbed by the skin and ofleaving no bothersome unctuous cream, contrary to the cream andregardless of the type of emulsion.

To prepare the lotion, the fatty phase constituents, such as paraffin,isopropyl esters of fatty acids, and the combination of emulsifiers aremelted and heated to high temperature, for example of between 60° and80°, in conventional fashion. Sorbitol, glycerine, and magnesiumsulfate, along with the constituents of the aqueous phase, are dissolvedin water at high temperature. The phases are combined and emulsified.The active ingredient is added at lower temperature, for example between40° and 60°. Next, the mass is allowed to cool while stirring.

The active substance is very effectively absorbed by the lotionaccording to the invention, which exhibits excellent stability understorage. It is used, for example, to treat eczema, dermatitis,psoriasis, and intimation.

To heal or treat these disorders, the lotion according to the inventionmay be applied topically on the affected areas. The quantity of lotionapplied varies depending on the concentration of the active ingredient.In general, a suitable quantity is applied to the affected area severaltimes daily, depending on the seriousness of the disorder requiringtreatment.

Unless otherwise indicated, all quantities, portions, and percentagesare applied in relation to the total weight or quantity or to the totalweight of the preparations.

The following examples are intended to illustrate the invention, but ina non-limiting fashion.

Water-in-oil lotions are prepared in the following way: The fatty phaseconstituents, such as paraffin, fatty acid esters, and the emulsifiercombination are heated to approximately 80° C. in a mixer-homogenizerwhich can be placed under a vacuum. Next, the aqueous phaseconstituents, such as sorbitol, glycerine, and magnesium sulfate, alongwith the acids and buffering agents, are dissolved in a correspondingproportion in water at a temperature of about 80° C., and the aqueousphase is added to the fatty phase in the mixer. The mixture is cooled ina vacuum to about 40° C. and homogenized while stirring. The activesubstance is added at this temperature and the preparation is cooled toabout 25° C. while stirring and under a vacuum. The preservatives aredissolved, depending on their physical and chemical properties, eitherin the fatty phase at approximately 80° C., in the aqueous phase atapproximately 80°, or added to the preparation at about 40° C.

In the following examples, hydrocortisone-21-acetate-17-propionate isused as the corticosteroid.

EXAMPLE 1

The water-in-oil lotion was prepared by using the followingconstituents:

    ______________________________________                                                                % by weight                                           ______________________________________                                        methoxypolyethylene glycol/dodecylglycol copolymer                                                      3.0                                                 (Elfacos E 200)                                                               hydroxyoctacosanyl hydroxy stearate (Elfacos C 26)                                                      2.5                                                 polyethylene glycol/dodecylglycol copolymer                                                             5.0                                                 (Elfacos St 9)                                                                isopropyl palmitate       11.0                                                synthetic squalene        2.0                                                 liquid paraffin           10.0                                                70% sorbitol (Karion F)   1.0                                                 hydrocortisone-21-acetate-17-propionate                                                                 0.200                                               butyl hydroxytoluene      0.05                                                benzyl alcohol            0.5                                                 phenoxyethanol            0.5                                                 citric acid               q.s. (to adjust                                                               the pH to 4-5)                                      demineralized water       to 100.00                                           ______________________________________                                    

The preparation was produced using the procedure detailed above. Thepreservative, phenoxyethanol, was dissolved in the aqueous phase, andthe anti-oxidant, butyl hydroxytoluene, was dissolved in the fattyphase. The active substance, hydrocortisoneaceponate, was dissolved inbenzylic alcohol and added to the lotion at a temperature ofapproximately 40° C.

EXAMPLE 2

A water-in-oil lotion was prepard by using the constituents listedbelow:

    ______________________________________                                                              % by weight                                             ______________________________________                                        fatty acid ester saturated with glycerol sorbitan                                                     1.5                                                   (Arlacel 986)                                                                 polyethoxylated fatty acids (Arlacel 989 or                                                           3.0                                                   Cremophor WO 7)                                                               isopropylmyristate      5.0                                                   liquid paraffin         11.0                                                  1,3-butylene glycol     3.0                                                   magnesium sulfate, heptahydrate                                                                       0.5                                                   hydrocortisone-21-acetate-17-propionate                                                               0.127                                                 benzyl alcohol          1.0                                                   demineralized water     to 100.00                                             ______________________________________                                    

EXAMPLE 3

A water-in-oil lotion was prepard by using the constituents listedbelow:

    ______________________________________                                                               % by weight                                            ______________________________________                                        polyoxypropylene-polyoxyethylene-glycerol-sorbitan                                                     4.0                                                  hydroxyisostearate (Arlacel 780)                                              polyethoxylated fatty acids (Arlacel 989)                                                              2.0                                                  isopropyl myristate      7.0                                                  octyldodecanol           5.0                                                  liquid paraffin          13.5                                                 glycerine                2.5                                                  70% sorbitol (Karion F)  2.5                                                  hydrocortisone-21-acetate-17-propionate                                                                0.127                                                phosphatidyl choline     3.0                                                  benzalkonium chloride    0.25                                                 lactic acid              q.s. (to adjust the                                                           the pH to 4-5)                                       demineralized water      to 100.00                                            ______________________________________                                    

EXAMPLE 4

    ______________________________________                                                               % by weight                                            ______________________________________                                        glycerol sorbitan oleostearate (Arlacel 481,                                                           2.0                                                  ICI Company)                                                                  polyethoxylated fatty acids (Arlacel 989,                                                              6.0                                                  ICI Company)                                                                  decyl oleate (Cetiol C, Henkel Company)                                                                15.0                                                 branched-chain paraffin (Arlamol HD, ICI Company)                                                      8.0                                                  microwax                 1.0                                                  glycerine                4.0                                                  magnesium sulfate, heptahydrate                                                                        0.70                                                 sodium salt of sorbic acid                                                                             0.20                                                 hydrocortisone-21-acetate-17-propionate                                                                0.05                                                 diammonium hydrogenocitrate                                                                            0.10                                                 citric acid              q.s. (to adjust the                                                           PH to 4-5)                                           demineralized water      to 100.00                                            ______________________________________                                    

I claim:
 1. A water-in-oil lotion comprisinghydrocortisone-21-acetate-17-propionate and a composition selected fromthe group consisting of A, B, C, and D each consisting of water-in-oilemulsifiers a) to d):wherein A. is:

    ______________________________________                                        Emulsifier combination a) % by weight                                         ______________________________________                                        a.sub.1 :methoxypolyethylene glycol/dodecylglycol polymer                                               1-10                                                a.sub.2 :hydroxyoctacosanyl hydroxystreate                                                              0.5-10                                              a.sub.3 :polyethylene glycol/dodecylglycol copolymers                                                   1-10                                                esters of fatty acids and/or fatty alcohols                                                             1-30                                                liquid paraffin           1-30                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                hydrocortisone-21-acetate-17-propionate                                                                 0.001-3                                             preservative              0-2.5                                               water                     50-85                                               ______________________________________                                    

wherein B. is:

    ______________________________________                                        Emulsifier combination b)                                                     ______________________________________                                        b.sub.1 :esters of fatty acids saturated with glycerol sorbitan                                           0.5-10                                            b.sub.2 :polyethoxylated fatty acids                                                                      1-7.5                                             esters of fatty acids and/or fatty alcohols                                                               1-30                                              liquid paraffin             1-30                                              glycerine or sorbitol solution (70% by weight)                                                            1-10                                              magnesium sulfate, heptahydrate                                                                           0.1-2                                             hydrocortisone-21-acetate-17-propionate                                                                   0.001-3                                           preservative                0-2.5                                             water                       50-85                                             ______________________________________                                    

wherein C. is:

    ______________________________________                                        Emulsifier combination c)                                                     ______________________________________                                        c.sub.1 :polyoxypropylene-polyoxyethylene-glycerol-sorbitan-                                               0.5-10                                           hydroxyisostearate                                                            c.sub.2 :polyethoxylated fatty acids                                                                       0.5-7.5                                          esters of fatty acids and/or fatty alcohols                                                                1-30                                             liquid paraffin              1-30                                             glycerine or sorbitol solution (70% by weight)                                                             1-10                                             magnesium sulfate, heptahydrate                                                                            0.1-2                                            hydrocortisone-21-acetate-17-propionate                                                                    0.001-3                                          preservative                 0-2.5                                            water                        50-85                                            ______________________________________                                    

wherein D. is:

    ______________________________________                                        Emulsifier combination d)                                                     ______________________________________                                        d.sub.1 glycerol sorbitan oleostearate                                                                   0.5-7.5                                            d.sub.2 :polyethoxylated fatty acids                                                                     0.5-10                                             esters of fatty acids and/or fatty alcohols                                                              1-30                                               liquid paraffin            1-30                                               glycerine or sorbitol solution (70% by weight)                                                           1-10                                               magnesium sulfate, heptahydrate                                                                          0.1-2.0                                            hydrocortisone-21-acetate-17-propionate                                                                  0.001-3                                            preservative               0-2.5                                              water                      50-85                                              ______________________________________                                    

in combination with cosmetically acceptable additives, and, in additionto the emulsifying combination indicated, one or a of the otherconstituents a₁ to d₂ or one or several of the emulsifying combinationsa) to d).
 2. The lotion according to claim 1, containing the followingconstituents:

    ______________________________________                                        A'                                                                            Emulsifier combination a) % by weight                                         ______________________________________                                        a.sub.1 : methoxypolyethlene glycol/dodecyglycol polymer                                                 2-7.5                                              a.sub.2 : hydroxyoctacosanyl hydroxystreate                                                             1-5                                                 a.sub.3 : polyethylene glycol/dodecylglycol copolymers                                                   2-7.5                                              esters of fatty acids and/or fatty alcohols                                                             1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        B'                                                                            Emulsifier combination b)                                                     ______________________________________                                        b.sub.1 : esters of fatty acids saturated with glycerol                                                  2-7.5an                                            b.sub.2 : polyethoxylated fatty acids                                                                   1-5                                                 esters of fatty acide and/or fatty alcohols                                                             1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        C'                                                                            Emulsifier combination c)                                                     ______________________________________                                        c.sub.1 : polyoxypropylene-poloxyethylene-glycerol-sorbitan-                                             2-7.5                                              hydroxyisostearate                                                            c.sub.2 : polyethoxylated fatty acids                                                                   1-5                                                 esters of fatty acids and/or fatty alcohols                                                             1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight                                                           1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                        D'                                                                            Emulsifier combination d)                                                     ______________________________________                                        d.sub.1 glycerol sorbitan oleostearate                                                                  1-5                                                 d.sub.2 : polyethoxylated fatty acids                                                                   2-8                                                 esters of fatty acids and/or fatty alcohols                                                             1-15                                                liquid paraffin           1-15                                                glycerine or sorbitol solution (70% by weight)                                                          1-10                                                magnesium sulfate, heptahydrate                                                                         0.3-1.5                                             hydrocortisone-21-acetate-17-propionate                                                                 0.01-2.5                                            preservative              0.2-1.5                                             water                     60-80                                               ______________________________________                                    


3. The lotion according to claim 1, wherein said lotion contains from0.0025 to 0.2% by weight hydrocortisone-21-acetate-17-alpha-propionate(hydrocortisoneaceponate).
 4. The lotion according to claim 1, havingthe following composition:

    ______________________________________                                                              % by weight                                             ______________________________________                                        fatty acid ester saturated with glycerol sorbitan                                                     1.5                                                   (Arlacel 986)                                                                 polyethoxylated fatty acids (Arlacel 989 or                                                           3.0                                                   Cremophor WO7)                                                                isopropyl myristate     5.0                                                   liquid paraffin         11.0                                                  1,3-butylene glycol     3.0                                                   magnesium sulfate, heptahydrate                                                                       0.5                                                   hydrocortisone-21-acetate-17-propionate                                                               0.127                                                 benzyl alcohol          1.0                                                   demineralized water     to 100.00                                             ______________________________________                                    